Chemical Changes in Brain Identify Autism

Action Points

Children with autism spectrum disorders have chemical changes in the brain between the ages of 3 and 10 that distinguish them from children with other forms of developmental delay.

At ages 3-4, children with ASD had lower concentrations of N-acetylaspartate, choline, and creatine, in both white and gray matter, although those lower concentrations were no longer seen at ages 9 and 10.

Children with autism spectrum disorders (ASD) have brain chemical changes between the ages of 3 and 10 that distinguish them from children with other forms of developmental delay, researchers reported.

In particular, concentrations of N-acetylaspartate, which plays important roles in several brain functions, rises over time to near-normal levels in ASD children, according to Stephen Dager, MD, of the University of Washington in Seattle, and colleagues.

In contrast, the compound remains at a low concentration in children with non-autism developmental delays, Dager and colleagues reported online in JAMA Psychiatry.

The pattern of changes of several other brain chemicals also differed between the groups, and between both groups and children with typical development, in a study that combined longitudinal and cross-sectional features, the investigators reported.

The findings suggest that "a dynamic brain developmental process underlies ASD," Dager and colleagues argued, while developmentally delayed children had a "different, more static" pattern of changes.

In the case of the ASD children, the investigators said, the dynamic pattern they observed beginning at age 3 or 4 "likely reflect a process that begins at an earlier stage of development."

To help fill the gap, they used proton magnetic resonance spectroscopy to scan 122 children with ASD, developmental delays, or typical development in three age groups -- ages 3 and 4, ages 6 and 7, and ages 9 and 10.

The ASD and developmentally delayed children were scanned over time, although not all were scanned at each time point, but the children with typical development were mainly scanned cross-sectionally, the authors reported.

The main outcome measures were concentrations of N-acetylaspartate, choline, creatine, myo-inositol, and glutamine plus glutamate in both gray and white matter of the brain at each time point, as well as calculation of rates of change between 3 and 10.

Dager and colleagues scanned 73 children at 3 or 4, including 45 with ASD, 14 with developmental delays, and 14 with typical development. At 6 and 7, they scanned 69 children, including 35 with ASD, 14 with developmental delays, and 20 with typical development, while at 9 and 10, they scanned 77 children, including 29 with ASD, 15 with delayed development, and 33 with typical development.

At the early age, they reported, children with ASD had lower concentrations of N-acetylaspartate, choline, and creatine, in both white and gray matter, than the children who were developing typically.

Those lower concentrations were no longer seen when the children were 9 and 10, Dager and colleagues found, and in particular N-acetylaspartate concentrations rebounded to nearly normal levels.

In contrast, the developmentally delayed children also had lower concentrations of N-acetylaspartate than the typical children at 3 and 4, but the levels remained low, at least in the gray matter, through the age of 10.

The pattern of changes in the ASD children, Dager and colleagues argued, is "comparable" with what happens in other disorders, such as multiple sclerosis, epilepsy, and traumatic brain injury, where the N-acetylaspartate level is reduced at the time of onset or insult and rebounds with treatment or recovery.

The rapid increase of N-acetylaspartate levels in ASD suggests "a dynamic and recoverable disease process that can result in other downstream effects but does not, in itself, persist over time," they argued.

The researchers cautioned that they had relatively few children with typical development in the youngest age group. Another limitation, they noted, is the primarily cross-sectional analysis of the typical children.

The study was supported by the National Institutes of Health.

The journal said the authors did not make any disclosures.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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